We will use recombinant DNA technology to select cDNA clones that can improve diagnosis of small cell tumors. These cancers include oat cell carcinoma, many of the non-Hodgkin's lymphomas, Ewing's sarcoma, small cell tumors of neuroectodermal origin, embryonal rhabdomyosarcoma, and the leukemias. In many cases the tumor cells are primitive cells which may be difficult to classify because there is no evidence of features of maturation. Yet proper classification is important since treatment is often different depending upon the cell type of the tissue of origin for the malignant cells. It is now possible to use recombinant DNA techniques to create hybridization probes, which can assay mRNA species present in one cell type and not another. In theory, immunodiagnostic approaches also are capable of assaying any gene product in which two malignant cell types may differ, but only recombinant DNA techniques offer the ability to efficiently select the crucial gene product even if it is a rare mRNA species unique to only one of the two cell types. In earlier work we selected a panel of clones corresponding to abundant mRNAs strongly regulated during myeloid differentiation. These clones will be useful in distinguishing between myeloid and lymphoid cells. We expect that some members of this panel of clones may also be useful in distinguishing any hematopoietic cell from cells of other lineages. We will use the new hybridization-subtraction recombinant DNA technology to select additional cDNA clones which can improve the differential diagnosis of the small cell tumors. This approach, if successful, will improve subclassification of other cancer cell types so that the most effective treatment can be selected. (2)